12-11775163-T-C

Variant names:

• chr12-11775163-T-C
• rs2723829
• NM_001987.5:c.163+22584T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001987.5(ETV6):​c.163+22584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,040 control chromosomes in the GnomAD database, including 20,654 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (20654 hom., cov: 32)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 5 publications found

Genes affected

ETV6 (HGNC:3495): (ETS variant transcription factor 6) This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]

ETV6 Gene-Disease associations (from GenCC):

• thrombocytopenia 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• acute myeloid leukemia

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics
• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001987.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV6	NM_001987.5	MANE Select	c.163+22584T>C		intron	N/A	NP_001978.1
	ETV6	NM_001413913.1		c.160+22584T>C		intron	N/A	NP_001400842.1
	ETV6	NM_001413914.1		c.136+22584T>C		intron	N/A	NP_001400843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV6	ENST00000396373.9	TSL:1 MANE Select	c.163+22584T>C		intron	N/A	ENSP00000379658.3
	ETV6	ENST00000545027.1	TSL:5	c.79+22584T>C		intron	N/A	ENSP00000441463.1
	ETV6	ENST00000541426.1	TSL:4	n.347+22584T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73283 AN: 151922 Hom.: 20648 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.482 AC: 73292 AN: 152040 Hom.: 20654 Cov.: 32 AF XY: 0.482 AC XY: 35791 AN XY: 74314

African (AFR) AF: 0.170 AC: 7051 AN: 41492

American (AMR) AF: 0.668 AC: 10208 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2083 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2673 AN: 5162

South Asian (SAS) AF: 0.421 AC: 2026 AN: 4818

European-Finnish (FIN) AF: 0.589 AC: 6221 AN: 10560

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41168 AN: 67952

Other (OTH) AF: 0.500 AC: 1056 AN: 2112

Alfa AF: 0.568 Hom.: 20210

Bravo AF: 0.480

Asia WGS AF: 0.445 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.53
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2723829; hg19: chr12-11928097;